Azadirachta / Neemboom


De neemboom 
onderzoek van Isa Servaes herboristen opleiding Syntra 1ste jaar 2014 - 2015

Mijn werk gaat over de “neem” (uitspraak:  “niem”) of “nim”, officiële naam “Azadirachta Indica”, een tropische, immer groene boom of struik uit de familie “Meliaceae”. Deze ‘wonderboom’ groeit snel tot zeer snel; op een jaar tijd kan hij een hoogte van 3 tot 4 meter hebben. Hij wordt meer dan 200 jaar oud. De bloemen lijken op seringen,  bijen en andere insecten houden van de geur.
De vruchten lijken op kleine langwerpige hazelnootjes, de kiemkracht is van heel korte duur.
Men kan alleen het heel verse zaad gebruiken om te planten.
De neemboom is voornamelijk afkomstig uit India, maar men vindt hem tegenwoordig in vele gebieden met tropisch en subtropisch klimaat verspreid over alle continenten.
Het woord “neem” komt uit het Sanskriet, en betekent “heilbrenger en genezer van ziekte”.
Deze boom speelt sedert mensenheugenis een zeer belangrijke rol in de ayurvedische geneeskunde.

Wat vertellen de boeken ?  Deze geven vrij uiteenlopende beschrijvingen en toepassingen, maar over één zaak zijn ze het wel eens: de neemboom is een zegen van de natuur.

1) Veeris, D. (2010). ‘Afrikantje’ en 99 andere kruiden. (2de druk). Rotterdam: Uitgeverij De Driehoek.
Neem is bevorderlijk voor de gezondheid.
Uit het zaad wordt olie of poeder gewonnen, die in de cosmetica gebruikt worden.
Deze olie en poeder worden gebruikt als middel tegen droge huid en haarproblemen, zoals hoofdluis.
De olie (en ook de bladeren in hun geheel) is (zijn) ook een bestrijdingsmiddel tegen insecten.
De stokjes worden door de Indiase bevolking als tandenborstel gebruikt.
Van nimbladeren wordt een thee getrokken die bloeddrukverlagend werkt.
Van de takken maakt men ook thee die zeer efficiënt is tegen jeuk.

2) Lad, Dr. V. & Frawley, Dr. David (1994). Ayurveda en kruiden. (2de druk). Amsterdam: Uitgeverij Schors.
De delen van de plant die worden gebruikt, zijn de schors en de bladeren.
De werkingen: bittertonisch, koortsverdrijvend, alteratief (bloedzuiverend), wormdrijvend, antiseptisch, braakonderdrukkend.
Indicaties: huidziekten (netelroos, eczeem, ringworm), parasieten, koorts, malaria, hoesten, dorst, misselijkheid, braken, diabetes, tumors, zwaarlijvigheid, artritis, reuma, geelzucht.
Bereiding: infusie (warm of koud), afkooksel, poeder, pasta, medicinale ghee, olie.
Neem is een sterk bloedzuiverend en ontgiftend middel.
Het kruid koelt koorts af.
Zorgt dat de gifstoffen in verband met ontstoken huidziekten of zwerende slijmvliezen verwijderd worden.
Neem is een zeer krachtig koortswerend middel bij malaria, het wordt in die toepassing meestal gecombineerd met zwarte peper en gentiaan.
Neem heeft ook een samentrekkende werking die het geneesproces ondersteunt.
Men moet zeer voorzichtig zijn wanneer er sprake is van ernstige vermoeidheid of vermagering van de patiënt.
In de vorm van olie is het een van de beste helende en desinfecterende middelen voor huidziekten, en daarbij is het ook nog ontstekingsremmend bij gewrichts-en spierpijn.

3) Houdret, J. (2001). Minibijbel Kruiden kweken. (7de druk). Utrecht: Veltman Uitgevers.
Neem heeft ontstekingsremmende en insectwerende eigenschappen.
Het werkt ook koortsverlagend, en wordt zeer graag gebruikt bij behandeling van malaria en lepra.
Uitwendig gebruik is zeer efficiënt bij huidproblemen, ontstekingen, oog-en oorklachten.
De twijgen worden als tandenborstel gebruikt.
De olie wordt in tandpasta, zeep en haarlotions verwerkt omwille van de zuiverende werking.
Neemextract zou ook haaruitval tegengaan. 
Het is in ieder geval een zeer efficiënt middel tegen steekmuggen en andere insecten (de bladeren houden deze diertjes op afstand). 

Ook op verschillende websites wordt de loftrompet bovengehaald.
http://www.pharmaresearchlibrary.com/
http://www.herbcyclopedia.com/item/health-benefits-of-neem-azadirachta-indica-2
http://www.neemfoundation.org
http://www.infinityfoundation.com/mandala/t_es/t_es_agraw_neem.htm 

Heilzame kenmerken die aan de neem worden toegeschreven zijn (onder meer):
anthelmintica (tegen parasitaire wormen), 
anti yeast (tegen gist en schimmel),
middel tegen ulcera (zweren),
antifertiliteitswerking (contraceptie),
middel tegen filariasis (tropische draadworm),
antifungaal (tegen schimmels),
antiviraal,
diureticum,
antihyperglycemisch (tegen te hoge suikerwaarden in het bloed),
anti-inflammatoir,
tegen malaria,
antinematodaal (tegen rondwormen),
antipyretisch (koortsverlagend),
antispermatogeen (voorkomt productie van zaadcellen),
hypercholesterolemisch,
krampstillend,
insecticide,
antitumor,
tegen hypoglycemie (te lage suikerwaarden in het bloed),
immunomodulator 

Er is echter onvoldoende onderzoek gedaan naar de vermeende voordelen van neem.  Bij volwassenen is het  gebruik van neem op korte termijn veilig, maar op lange termijn kan het gebruik  de nieren of lever schaden. Bijkomend onderzoek is, gezien de vele positieve eigenschappen, zeker aangewezen, vandaar dat bijvoorbeeld ook de Neem Foundation werd opgericht.



Azadirachta indica : A herbal panacea in dentistry - An update

T Lakshmi1, Vidya Krishnan2, R Rajendran3, N Madhusudhanan4
1 Department of Pharmacology, Saveetha Dental College and Hospital, Velappanchavadi, Chennai, India
2 Department of Oral Medicine, SRM Dental College, Kattankulathur, Tamil Nadu, India
3 Green Chem Herbal Extracts and Formulations, Bangalore, Karnataka, India
4 Department of Pharmacology, Sathyabama Dental College, Chennai, Tamil Nadu, India

   Abstract
Azadirachta indica commonly known as Neem, is an evergreen tree. Since time immemorial it has been used by Indian people for treatment of various diseases due to its medicinal properties. It possesses anti-bacterial, anti-cariogenic, anti-helminthic, anti-diabetic, anti-oxidant, astringent, anti-viral, cytotoxic, and anti-inflammatory activity. Nimbidin, Azadirachtin and nimbinin are active compounds present in Neem which are responsible for antibacterial activity. Neem bark is used as an active ingredient in a number of toothpastes and toothpowders. Neem bark has anti-bacterial properties, it is quite useful in dentistry for curing gingival problems and maintaining oral health in a natural way. Neem twigs are used as oral deodorant, toothache reliever and for cleaning of teeth. The objective of this article is to focus on the various aspects of Azadirachta indica in dentistry in order to provide a tool for future research.

Keywords: Azadirachta indica , anti-bacterial, anti-cariogenic, oral healt
Neem has been extensively used in Ayurveda, Unani and Homoeopathic medicine and has become a wonder tree of modern medicine. [1] It has been used traditionally for the treatment of inflammation, infections, fever, skin diseases and dental problems.

It is effective in several epidermal dysfunctions such as acne, psoriasis, eczema. Neem leaves have been reported to also possess antihyperglycemic, [2] immunomodulatory, [3] anti-inflammatory, [4] antimalarial, [5] antioxidant, [6] antiviral, [7] antimutagenic [8] and anticarcinogenic [9] properties. Neem also exhibits antibacterial, [10] antifungal, [11] hepatoprotective, [12] anti-ulcer, [13] anti-fertility and anti-nociceptive activity. [14],[15]

Neem twigs are used as oral deodorant, toothache reliever and for cleaning of teeth. Neem bark possesses antibacterial and deodorant activity. The phytochemical constituents present in neem are nimbidin, nimbin, nimbolide, Azadirachtin, gallic acid, epicatechin, catechin, and margolone. All these exhibit potent antibacterial activity. The chief active constituent of neem is azadirachtin, which is an effective antimicrobial agent. [15],[16] Neem has also been traditionally used as a skin moisturizer. [17]

Objective of the literature review

Azadirachta indica is an evergreen tree having potential medicinal values. It has been found to be active against many dreadful disorders like hepatitis, viral infections, malaria and cancer. It is also effective against periodontal pathogens, and oral acidogenic bacteria responsible for dental caries and dental plaque. The aim of the present review is to focus on the dental aspects of various parts of Neem extract with their chemical constituents and biological activities. Several traditional uses of the miraculous tree have also been briefly discussed. This information may give a bird's eye view for the dentist, and consequently this database might play a major role in future research in the field of dentistry 

Therapeutic role of Azadirachta indica in dentistry

Nimbidin, a major active principle isolated from seed kernels of A. indica exhibits several biological actions. From nimbidin other active constituents like nimbin, nimbinin, nimbidinin, nimbolide and nimbidic acid have been isolated which are responsible for its biological activities. [16]
Neem dental care products contains Neem leaf or bark extract. Neem leaf is rich in antioxidants and helps to boost the immune response in gum and tissues of the mouth. [18],[19] Neem offers a good remedy for curing mouth ulcers, tooth decay and acts as a pain reliever in toothache problems.

Dental applications of Neem

Antibacterial activity

Neem is a natural antibacterial agent. Various scientific studies have revealed its antibacterial activity. [20] The antimicrobial effects of Neem have been reported against S. mutans and S. faecalis. [21] Ethanolic extract of Neem leaves and sticks and bark exhibited significant antibacterial activity. [22],[23] Dried chewing sticks of Neem showed maximum antibacterial activity against S. mutans compared to other dental caries-causing organisms, S. salivarius, S. mitis, and S. sanguis. [24]

Anti-candidial activity

Ethanolic and aqueous extract of Neem leaf showed significant anti-candidial effect against C. albicans. [25] A clinical study demonstrated the effects of the leaf aqueous extract from Azadirachta indica (Neem) on adhesion, cell surface hydrophobicity and biofilm formation, which may affect the colonization by Candida albicans. The results suggest that Neem leaves have a potential anti-adhesive effect on the sample studied in vitro. [26]

Anti-cariogenic activity

Mango and Neem extract showed antimicrobial activity against S. mutans, S. salivarius, S. sanguis and S. mitis. A combination of chewing sticks is found to be beneficial in eradicating the dental caries-causing organism. [27] Chloroform extract of Neem leaf inhibited Streptococcus mutans and Streptococcus salivarius and provides an aid for treating dental caries. [28] Antimicrobial activity of commercially available Himalaya herbal dental cream containing neem and fluoride-containing cheerio gel toothpaste has been assessed in school children. The study reported both the toothpastes showed a good antimicrobial effect on caries producing salivary streptococcus mutans. [29] The toothpaste containing Neem as well as fluoridated toothpaste were equally efficacious against caries-producing bacteria. Acetone extract from the bark of Neem is bactericidal against S. sobrinus hence indicates its anti-cariogenic activity. [30]

Anti-plaque activity

Aqueous extract of Neem stick and the gallotannin-enriched extract from Melaphis chinensis inhibited insoluble glucan synthesis and results in bacterial aggregation. It reduces the ability of streptococci to colonize tooth surfaces. [31] Neem oil shows significant antibacterial activity and has been suggested for use in treating dental plaque. [32] Mucoadhesive dental gel containing Azadirachta indica is found to be beneficial in reducing the plaque index and salivary bacterial count comparatively better than chlorhexidine gluconate mouthwash. [33]

Efficacy of Neem extract against acidogenic oral bacteria in fixed orthodontic appliance patients

The primary acid-tolerant bacteria associated with dental plaque including Streptococcus mutans, Streptococcus oralis, Streptococcus sobrinus, Lactobacillus acidophilus, Streptococcus salivarius, Streptococcus mitis, Streptococcus sangui, Streptococcus intermedius, and Streptococcus anginosus that surround orthodontic appliances are a common problem in many patients undergoing orthodontic treatment. It has also been reported that presence of fixed orthodontic appliance greatly inhibits oral hygiene and creates new retentive areas for plaque and debris.

Ethanolic leaf extract of Azadirachta indica shows significant antibacterial activity against selected acidogenic oral bacteria causing dental plaque in fixed orthodontic appliance patients. The study conducted by us evaluated the anti-plaque activity of the extract against S. mutans, S. sanguis, and S. mitis. The extract did not inhibit L. acidophilus when tested. [34]

Efficacy against periodontal pathogens

Brushing with Neem toothpaste after every meal and using a mouthwash with Neem extract is recommended treatment for preventing gingivitis. In a study, Neem-based mouth rinse was given to patients for assessing anti-plaque and anti-gingivitis activity. The findings conclude that Neem mouth rinse is as effective as chlorhexidine in reducing periodontal indices. Neem stick is found to be effective as a toothbrush in reducing dental plaque and gingival inflammation. [35]

Studies indicate that leaf extract of A. indica-based mouth rinse is highly efficacious and that it may be used as an alternative therapy in the treatment of periodontal disease. [36] Gingivitis has been prevented or even reversed with regular use of Neem toothpaste and mouthwash. Shefali sharma conducted a study on Soluneem (a water-soluble formulation from the Neem seed kernel from Shefali sharma conducted a study on Soluneem (a water-soluble formulation from the Neem seed kernel from Azadirachta Indica containing Azadirachtin) as an antimicrobial agent and the effective concentration of Soluneem required to inhibit periodontopathic bacteria and to compare it with a known antiplaque agent chlorhexidine (0.2%) in vitro. Study revealed that soluneem extract did not show activity against the organisms (Bacteroids fragilis, B. distatonics, Prevotella corporis, Prevotella melagingogenica, Pepto streptococcus species) tested. [37]

Also Botelho et al., and Behl et al., in their experiments and trials concluded that Azadirachta indica is highly efficacious in the treatment of periodontal disease thus exhibiting its biocompatibility with human periodontal fibroblast. [38]

Neem as root canal irrigant

Sodium hypochlorite has been used as root canal irrigant for decades; it causes potential weakening of the tooth structure by decreasing the hardness and structural integrity of the dentin within the root canal. To overcome this disadvantage herbal drugs are used effectively to inhibit E. faecalis that causes root canal failure in patients undergoing endodontic treatment.

Aqueous and ethanolic extract of Neem leaf inhibits S. mutans and E. faecalis which cause root canal failure in endodontic procedure. Its antioxidant and antimicrobial properties makes it a potential agent for root canal irrigation as an alternative to sodium hypochlorite. [23] Literature suggested that the Neem (Azadirachta indica) leaf extract has significant antimicrobial effect against E. faecalis derived from infected root canal samples. The extract was found to be efficacious compared with 2% sodium hypochlorite.

Neem in dental care industry

Various parts of the Neem tree possess astringent and antiseptic activity. Leaf extracts have been widely used in both traditional and conventional times to manufacture toothpaste and mouthwash in the oral care dentistry. Its antibacterial properties due to the presence of nimbidin, Azadirachtin, and nimbinin help to remove many oral aerobic and anaerobic pathogens existing in the oral cavity.

Neem bark and leaf extract is most effectively used in preventing cavities and gum disease. Mouthwash containing Neem is a remedy for tooth decay, oral infections, prevents bleeding and sore gums. Twigs of Neem tree are used as chewing sticks by people all over India.

   Conclusion

Regular brushing with Neem-containing toothpaste will reduce the deposition of plaque, prevents caries, and enhances the immune response for overall oral health. Frequent usage of mouthwash containing Neem extract will lessen gingival problems, and also treats halitosis.

In this modern, trendy world, we have done enough damage to nature. It is high time we start changing ways, to synchronize ourselves with nature, providing ample space for each other. Here we are trying to retrieve and learn the ancient Indian ways, which can still be infused into our fast-paced lives for a good effect, benefitting our future generations to come. This article hopes to lay a good solid base for further uses of one of nature's best gift-Neem in many more day-to-day functions. If education can be provided in dental and dental hygiene schools about the use of Neem-based and also herbal oral care products, it would help our dentists treat patients more holistically.

References
1.

Athavale VB. Dentistry in Ayurveda [Danta-Shastra]. New Delhi: Chaukhamba Sanskrit Pratishthan; 1999.

2.
Khosla P, Bhanwra S, Singh J, Seth S, Srivastava RK. A study of hypoglycaemic effects of Azadirachta indica (Neem) in normaland alloxan diabetic rabbits. Indian J Physiol Pharmacol 2000;44:69-74.

3.
van der Nat JM, Klerx JP, van Dijk H, de Silva KT, Labadie RP. Immunomodulatory activity of an aqueous extract of Azadirachta indicastem bark. J Ethnopharmacol 1987;19:125-31.
4.
Tidjani MA, Dupont C, Wepierre J. Antiinflammatory activity of Azadirachta indica. Planta Med Phytother 1989;23:259-66.

5.
Dhar R, Zhang K, Talwar GP, Garg S, Kumar NJ. Inhibition of the growth and development of asexual and sexual stages of drug-sensitive and resistant strains of the human malaria parasite Plasmodium falciparum by Neem (Azadirachta indica) fractions. J Ethnopharmacol 1998;61:31-9.

6.
Rao AD, Devi KN, Thyagaraju KJ. Ayurtox for body Detoxification. Enzyme Inhib 1998;14:85-6.

7.
Rao AR, Sukumar S, Paramasivam TV, Kamalakshi S, Parashuraman AR, Shantha M. Study of antiviral activity of tender leaves of Margosa tree (Melia azadericta) on vaccinia and variola virus: A preliminary report. Indian J Med Res 1969;57:495-502.

8.
Balasenthil S, Arivazhagan S, Ramachandran CR, Ramachandran V, Nagini S. Chemopreventive potential of neem (Azadirachta indica) on 7, 12-dimethylbenz (a) anthracene (DMBA) induced hamster buccal pouch carcinogenesis. J Ethnopharmacol 1999;67:189-95.

9.
Arivazhagan S, Balasenthil S, Nagini S. Modulatory effects of Garlic and Neem leaf extracts on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced oxidative stress in Wistar rats. Cell Biochem Funct 2000;18:17-21.

10.
Baswa M, Rath CC, Dash SK, Mishra RK. Antibacterial activity of Karanj (Pongamia pinnata) and Neem (Azadirachta indica) seed oil: A preliminary report. Microbios 2001;105:183-9.

11.
Jacobson M. Pharmacological and toxicological effects of Neem and China berry on Warm blooded animals. Neem Newslett 1986;3:39-43.

12.
Bhanwra S, Singh J, Khosla P. Effect of Azadirachta Indica (Neem) leaf aqueous extract on paracetamol-induced liver damage in rats. Indian J Physiol Pharmacol 2000;44:64-8.

13.
Bandyopadhyay U, Chatterjee R, Bandyopadhyay R. US Patent 5,730,986, 1998; corresponding to Indian Patent 1100/Del/95.

14.
Saimbi CS. The efficacy of neem extract -Reported in Jeevaniya Health Care Magazine 1994. Available from: http://www.healthmantra.com/Hctrust/Art6.Shtml. [Accessed at 2013 Oct].

15.
Bhanwara, S, Singh J, Khosla P. Antinociceptive activity of Azadirachta Indica (neem) in rats. Indian J Physiol Pharmacol 2000;18:17-21.

16.
Sharma P, Tomar L, Bachwani M, Bansal V, Review on Neem (Azadirechta indica):Thousand Problem One Solution, Int Res J Pharm 2011;2:97-102.

17.
Biswas K, Chattopadhyay I, Banerjee RK, Bandyopadhyay U. Biological activities and medicinal properties of Neem (Azadirachta Indica). Curr Sci 2002;82:1336-45.

18.
Kapoor S, Saraf S. Assessment of viscoelasticity and hydration effect of herbal moisturizers using bioengineering techniques. Pharmacogn Mag 2010;6:298-304.

19.
Subapriya R, Nagini S. Medicinal properties of neem leaves: A Review. Curr Med Chem Anticancer Agents 2005;5:149-6.

20.
Nayak A, Ranganathan N, Sowmya GB, Kishore B, Kudalkar M. Evaluation of antibacterial and anticandidial efficacy of aqueous and alcoholic effect of neem (Azadirachta Indica): An Invitro study. Int J Res Ayurveda Pharm 2011;2:230-5.

21.
Siswomihardjo W, Sunarintyas SB, Nishimura M, Hamada T. The difference of antibacterial effect of neem leaves and stick extract. Int Chin J Dent 2007;7:27-9.

22.
Almas K. The antimicrobial effects of extracts of Azadirachta Indica (Neem) and Salvadora Persica (Arak) chewing sticks. Indian J Dent Res 1999;10:23-6.
[PUBMED]
23.
Bohora A, Hegde V, Kokate S. Comparison of antibacterial efficacy of neem leaf extract and 2% sodium hypochlorite against E.Faecalis, C.Albicans and mixed culture- An In Vitro study. Endodontology 2010;22:8-12.

24.
Chava VR, Manjunath SM, Rajanikanth AV, Sridevi N. The efficacy of neem extract on four microorganisms responsible for causing dental caries viz Streptococcus Mutans, Streptococcus Salivarius, Streptococcus Mitis and Streptococcus Sanguis: An In Vitro study. J Contemp Dent Pract 2012;13:769-72.

25.
Dhanya Kumar NM, Sidhu P. The antimicrobial activity of Azardirachta Indica, Glycyrrhiza Glabra, Cinnamum Zeylanicum, Syzygium Aromaticum, Accacia Nilotica on Streptococcus Mutans And Enterococcus Faecalis-An In Vitro study. Endodontology. Available from: http://medind.nic.in/eaa/ t11/i1/eaat11i1p16.pdf. [Last accessed on 2013 Sep].

26.
Polaquini SR, Svidzinski TI, Kemmelmeir C, Gasparetto A. Effect of aqueous extract from Neem on hydrophobicity, biofilm formation and adhesion in composite resin by Candida albicans. Arch Oral Biol 2006;51:482-90.

27.
Prashant GM, Chandu GN, Murulikrishna KS, Shafiulla MD. The effect of mango and neem extract on four organisms causing dental caries: Streptococcus Mutans, Streptococcus Salivavius, Streptococcus Mitis, Andstreptococcus Sanguis: An In Vitro study. Indian J Dent Res 2007;18:148-51.
[PUBMED]
28.
Packia Lekshmi NCJ, Sowmia N, Viveka S, Raja Brindha J, Jeeva S. The inhibiting effect of Azadirachta indica against dental pathogens. Asian J Plant Sci Res 2012;2:6-10.

29.
Patil S, Venkataraghavan K, Anantharaj A, Patil S. Comparison of two commercially available toothpastes on the salivary Streptococcus Mutans count in urban preschool children -An In Vivo study. International Dentistry SA 2010;12:72-82.

30.
Bhuiyan MM, Nishimura M, Matsumura S, Shimonu T. Antibacterial effects of crude Azadirachta Indica neem bark extract on Streptococcus Sobrinus. Pediatr Dent J 1997;7:61-4.

31.
Wolinsky Le, Mania S, Nachnani S, Ling S. The inhibiting effect of aqueous Azadirachta Indica (Neem) extract upon bacterial properties influencing In Vitro plaque formation. J Dent Res 1996;75:816-22.

32.
Elavarasu S, Abinaya P, Elanchezhiyan S, Thangakumaran, Vennila K, Naziya KB. Evaluation of anti-plaque microbial activity of Azadirachta Indica (Neem Oil) In Vitro: A pilot study. J Pharm Bioallied Sci 2012;4:S394-6.

33.
Pai MR, Acharya LD, Udupa N. Evaluation of antiplaque activity of Azadirachta Indica leaf extract gel-A 6-week clinical study. J Ethnopharmacol 2004;90:99-103.

34.
Lakshmi T, Aravind Kumar S. Antibacterial evaluation of Azadirachta Indica ethanolic leaf extract against selected acidogenic oral bacteria causing dental plaque in fixed orthodontic appliance patients - An Invitro study. J Bot Res 2012;1:30-40.

35.
Bhambal A, Kothari AS, Saxena S, Jain M. Comparative effect of Neemstick And Toothbrush on plaque removal and gingival health - A clinical trial. J Adv Oral Res 2011;2:51-6.

36.
Chatterjee A, Saluja M, Singh N, Kandwal A. To evaluate the antigingivitis and antipalque effect of an Azadirachta Indica (Neem) mouthrinse on plaque induced gingivitis: A double-blind, randomized, controlled trial. J Indian Soc Periodontol 2011;15:398-401.
[PUBMED]
37.
Sharma S, Suchetha A, Vijayendra R, Bharwani AG. An In Vitro microbiological study evaluating the efficacy of soluneem (A water soluble Neem formulation from Azadirachta Indica) against periodontopathic microorganisms. J Oral Health Commun Dent 2012;6:4-9.

38.
Botelho MA, Santos RA, Martins JG, Carvalho CO, Paz MC, Azenha C, et al. Efficacy of a mouthrinse based on leaves of the neem tree (Azadirachta indica) in the treatment of patients with chronic gingivitis: A doubleblind, randomized, controlled trial. J Med Plant Res 2008;2:341-6.



 


Azadirachta indica A. Juss. monograph
/ Melia azadirachta
Linn. (Meliaceae)
English Names
Indian Lilac, Margosa Tree, Neem Tree
Sanskrit Name
Nimba
Hindi Name
Nim, Nimb

Habitat
It is commonly found throughout the greater part of India and often cultivated. Though not a forest-tree, it is generally found to grow wild.
A large, evergreen tree, with long, spreading branches forming a broad crown. The bark is grey and rough; the leaves are alternate, the leaflets 8-19, glossy and bluntly serrate; the flowers are white or pale-yellow, small, scented, numerous and found in long, axillary panicles; the drupes are yellow on ripening, aromatic, oblong and smooth, with a single exalbuminous seed.

Principal Constituents
The alcoholic extract of the fresh stem and bark yielded the bitter principles nimbin, nimbinin, and nimbidin. The alcoholic extract of the air-dried rootbark yielded nimbin and nimbidin. Another terpenic constituent, identical with sugiol, is reported to be present in the stem and bark. Petrol-ether soluble fraction of the alcoholic extract of the stem-bark yielded an essential oil (0.02%), having characteristics similar to the oil isolated from the blossoms. All parts of the plant yield ß-sitosterol1. The leaves contain nimbin, nimbinene, 6-desacetylnimbinene, nimbandiol, nimbolide and quercetin. The presence of ß-sitosterol, n-hexacosanol and nonacosane is also reported2. The diterpenoids margolone, nimbogone, nimbonolone and mimbolinin have been isolated from the plant3.

Pharmacology
A crude extract of the leaves was studied for its effects on the cardiovascualar system of anesthetized guinea pigs and rabbits. The extract (200mg/kg) decreased the heart-rate of the rabbit from 280 to 150 beats/min. It also exhibited a weak anti-arrhythmic activity in rabbit against ouabain-induced dysrhythmia4.

The leaves are reported to possess antifertility properties. The powder of the leaves at the dose level of 20mg, 40mg and 60mg/rat/day for 24 days exhibited spermicidal activity. The leaves are said to be used as an anthelmintic. The aqueous extract of leaves exhibited anti-ulcer and anti-inflammatory activity. The water soluble portion of the alcoholic extract of the leaves was found to possess a significant blood sugar lowering effect in glucose-fed and adrenaline-induced hyperglycemic rats but failed to show such effect in normal and streptozotocin induced diabetic rats. The freshly prepared leaf extract at low doses (10, 20, 50, 100 and 200mg/kg) produced a significant anti-anxiety effect whereas at higher doses (400mg and 800mg/kg) it did not show the activity. The acetone extract of leaves exhibited CNS depression, a reduction of blood pressure as well as heart rate without showing diuretic activity5.

Laboratory trials on rats have shown that the oil from the seed kernal and nimbidol in a dose of 8mg/kg body wt possess anti-arthritic action6.

Clinical studies
Clinical trials were conducted on 9 patients of congestive heart failure with anasarca to study the diuretic effect of sodium nimbidinate. 250mg were administered daily by deep intra-muscular injection in the gluteal region. The injections were repeated for 2-13 days with an average of about 5 injections per patient. Four other patients were also studied as controls on the same lines with bed rest, low sodium diet and adequate digitalization without any diuretic. Eight of the patients showed a definite diuretic response. The control group did not show any diuresis. No toxic reaction was noted except local discomfort or slight pain7.

Clinical trials were conducted on 12 cases of congestive cardiac failure with sodium nimbidinate for diuretic activity. Encouraging diuretic activity was observed with good response in 4 cases. There was no significant toxicity8.

Toxicity
A study of the toxicity of nimbidin on frogs showed that the average lethal dose was estimated at 0.25mg/g body wt.

Indications
Neem extracts have been reported to possess anti-diabetic, anti-bacterial and anti-viral properties. The stem, root, bark and young fruits are reported to possess astringent, tonic and anti-periodic properties. The bark is reported to be beneficial in malarial fever and useful in cutaneous diseases.

References
Indian Pat. NO.13343, 1927; Bhattacharji et. al., J sci industr Res, 1953, 12B, 154; Mitra et. al., ibid, 12B, 152; Sengupta et. al., Chem & Ind, 1958, 861; Narasimhan, Chem & Ind, 1957, 661.
Ketkar, 1976, 208; Troup, I, 180; Dastur, Useful Plants, 39; Mitra, C R , 6, 9, 64; Christopher, loc. cit.; Murthy, Indian Fmg, N S, 1957-58, 7(9), 9; Macmillan, 29; Basu & 6 Chakraborty, J Indian chem Soc, 1968, 45, 466; Chem Abstr,1981, 95, 111715; Awasthi & Mitra, Phytochemistry, 1971, 10, 2842; Nutritive Value of Indian Foods, 69; Dakshinamurti, Curr Sci, 1954, 23, 125.
Hanson, Nat Prod Rep, 1991, 54, 6.
Mitra, C R, 64, 96; Tyagi et. al., Nagarjun 1977-78, 21(4), 5; Basu, J Bombay nat Hist Soc, 1955-56, 53, 743; Rao et. al., Indian J med Res, 1969, 57, 495; Joshi & Magar, J sci industr Res, 1952, 11B, 261; Banerjee & Sanyal, Proc Indian Sci Congr, 1956, pt. III, 348; Shrivastava & Singh, Indian Drugs, 1981-82, 19, 245; Dictionary org Compds, V, 688; Thompson & Anderson, J pharm Sci, 1978, 67, 1467.
Qamar et.al., Pakist J Industr Res, 1989, 32, 600; Vedavathy et. al., Int J Pharmacogn 1991, 29, 113; Bhattarai, ibid, 1992, 30, 145; Shaikh, Curr Sci, 1993, 64, 688; Garg, et. al., Planta Med, 1993, 59, 215 Alam et. al., Fitoterapia, 1990, 61, 240; Chattopadhyay & Maitra, ibid, 1993, 64, 332; El-Hawary & Kholief, Arch Pharm Res, 1990, 13, 108; Handa, 1992, 63, 3; Jaiswal et. al., Indian J. Exp Biol, 1994, 32, 484; Chattopadhyay et. al., ibid, 1992, 738; Singh et. al., ibid, 1990, 61, 164.
Dastur, Useful Plants, 40; Mitra, Indian Oilseeds J, 1956-57, 1, 256;Information from Dr C R Mitra, NBRI, Lucknow; Shankaranarayanan & Sirsi, Indian J Pharm, 1961, 23, 53.
Shah et. al., Ind. J. Med. Sci., 1958, 12, 150.
Shah et. al., J. Assoc. Physician India, 1959, 7, 235.


 
Curr Med Chem Anticancer Agents. 2005 Mar;5(2):149-6.
Medicinal properties of neem leaves: a review.
Subapriya R1, Nagini S.
Azadirachta indica, commonly known as neem, has attracted worldwide prominence in recent years, owing to its wide range of medicinal properties. Neem has been extensively used in Ayurveda, Unani and Homoeopathic medicine and has become a cynosure of modern medicine. Neem elaborates a vast array of biologically active compounds that are chemically diverse and structurally complex. More than 140 compounds have been isolated from different parts of neem. All parts of the neem tree- leaves, flowers, seeds, fruits, roots and bark have been used traditionally for the treatment of inflammation, infections, fever, skin diseases and dental disorders. The medicinal utilities have been described especially for neem leaf. Neem leaf and its constituents have been demonstrated to exhibit immunomodulatory, anti-inflammatory, antihyperglycaemic, antiulcer, antimalarial, antifungal, antibacterial, antiviral, antioxidant, antimutagenic and anticarcinogenic properties. This review summarises the wide range of pharmacological activities of neem leaf.

J Am Mosq Control Assoc. 1999 Jun;15(2):133-52.
Activity and biological effects of neem products against arthropods of medical and veterinary importance.
Mulla MS1, Su T.
Botanical insecticides are relatively safe and degradable, and are readily available sources of biopesticides. The most prominent phytochemical pesticides in recent years are those derived from neem trees, which have been studied extensively in the fields of entomology and phytochemistry, and have uses for medicinal and cosmetic purposes. The neem products have been obtained from several species of neem trees in the family Meliaceae. Six species in this family have been the subject of botanical pesticide research. They are Azadirachta indica A. Juss, Azadirachta excelsa Jack, Azadirachta siamens Valeton, Melia azedarach L., Melia toosendan Sieb. and Zucc., and Melia volkensii Gürke. The Meliaceae, especially A. indica (Indian neem tree), contains at least 35 biologically active principles. Azadirachtin is the predominant insecticidal active ingredient in the seed, leaves, and other parts of the neem tree. Azadirachtin and other compounds in neem products exhibit various modes of action against insects such as antifeedancy, growth regulation, fecundity suppression and sterilization, oviposition repellency or attractancy, changes in biological fitness, and blocking development of vector-borne pathogens. Some of these bioactivity parameters of neem products have been investigated at least in some species of insects of medical and veterinary importance, such as mosquitoes, flies, triatomines, cockroaches, fleas, lice, and others. Here we review, synthesize, and analyze published information on the activity, modes of action, and other biological effects of neem products against arthropods of medical and veterinary importance. The amount of information on the activity, use, and application of neem products for the control of disease vectors and human and animal pests is limited. Additional research is needed to determine the potential usefulness of neem products in vector control programs.

Life Sci. 2004 Oct 29;75(24):2867-78.
Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer.
Bandyopadhyay U1, Biswas K, Sengupta A, Moitra P, Dutta P, Sarkar D, Debnath P, Ganguly CK, Banerjee RK.
We have shown earlier that Neem (Azadirachta indica) bark aqueous extract has potent antisecretory and antiulcer effects in animal models and has no significant adverse effect (Bandyopadhyay et al., Life Sciences, 71, 2845-2865, 2002). The objective of the present study was to investigate whether Neem bark extract had similar antisecretory and antiulcer effects in human subjects. For this purpose, a group of patients suffering from acid-related problems and gastroduodenal ulcers were orally treated with the aqueous extract of Neem bark. The lyophilised powder of the extract when administered for 10 days at the dose of 30 mg twice daily caused a significant (p < 0.002) decrease (77%) in gastric acid secretion. The volume of gastric secretion and its pepsin activity were also inhibited by 63% and 50%, respectively. Some important blood parameters for organ toxicity such as sugar, urea, creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, albumin, globulin, hemoglobin levels and erythrocyte sedimentation rate remained close to the control values. The bark extract when taken at the dose of 30-60 mg twice daily for 10 weeks almost completely healed the duodenal ulcers monitored by barium meal X-ray or by endoscopy. One case of esophageal ulcer (gastroesophageal reflux disease) and one case of gastric ulcer also healed completely when treated at the dose of 30 mg twice daily for 6 weeks. The levels of various blood parameters for organ toxicity after Neem treatment at the doses mentioned above remained more or less close to the normal values suggesting no significant adverse effects. Neem bark extract thus has therapeutic potential for controlling gastric hypersecretion and gastroesophageal and gastroduodenal ulcers.

J Dent Res. 1996 Feb;75(2):816-22.
The inhibiting effect of aqueous Azadirachta indica (Neem) extract upon bacterial properties influencing in vitro plaque formation.
Wolinsky LE1, Mania S, Nachnani S, Ling S.
The purpose of this investigation was to examine the inhibitory effects of aqueous extracts derived from the bark-containing sticks (Neem stick) of Azadirachta indica upon bacterial aggregation, growth, adhesion to hydroxyapatite, and production of insoluble glucan, which may affect in vitro plaque formation. Neem stick extracts were screened for minimal bacterial growth inhibition (MIC) against a panel of streptococci by means of a broth dilution assay. Initial bacterial attachment was quantified by the measurement of the adhesion of 3H-labeled Streptococcus sanguis to saliva-conditioned synthetic hydroxyapatite. The effect of the Neem stick extract upon insoluble glucan synthesis was measured by the uptake of radiolabeled glucose from 14C-sucrose. Aggregating activity of the Neem stick extracts upon a panel of streptococci was also examined. No inhibition of bacterial growth was observed among the streptococcal strains tested in the presence of < or = 320 micrograms/mL of the Neem stick extract. The pre-treatment of S. sanguis with the Neem stick extract or the gallotannin-enriched extract from Melaphis chinensis at 250 micrograms/mL resulted in a significant inhibition of the bacterial adhesion to saliva-conditioned hydroxyapatite. Pre-treatment of saliva-conditioned hydroxyapatite with the Neem stick or gallotannin-rich extract prior to exposure to bacteria yielded significant reductions in bacterial adhesion. The Neem stick extract and the gallotannin-enriched extract from Melaphis chinensis inhibited insoluble glucan synthesis. Incubation of oral streptococci with the Neem stick extract resulted in a microscopically observable bacteria aggregation. These data suggest that Neem stick extract can reduce the ability of some streptococci to colonize tooth surfaces.

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